The protein ricin extracted from castor seeds has been shown to be an effective anti-tumor agent. It has a sugar binding subunit which shows a high affinity for transformed cells and a toxin subunit which stops protein synthesis by enzymatically disrupting the ribosomal binding site for elongation factors. We have obtained excellent crystals of this toxin and have found at least one, and probably three, isomorphous heavy metal derivatives. We propose to solve the three dimensional structure of the protein by x-ray diffraction and to elucidate its mechanism of action by a number of stratagems. We propose to compare its structure with the similar toxin PAP already under structural investigation in this laboratory. We also propose to carry out a complementary biochemical program to define key catalytic residues, to screen for competitive inhibitors and to do "structural mapping" by partial proteolytic digestion. We anticipate that the structure and mechanism which should be elucidated by this study will further our knowledge of protein synthesis and may suggest a rationale basis for the design of anti-tumor agents.